Metastatic Spine Disease Research Articles

Clinical Rationale of Using Steerable Technologies for Radiofrequency Ablation Followed by Cavity Creation and Cement Augmentation in the Treatment of Painful Spinal Metastases

(1) Background: Cement distribution after radiofrequency ablation of spinal metastases can be unpredictable due to various tumor factors, and vertebral augmentation requires advanced devices to prevent cement leakage and achieve satisfactory filling. The purpose of this study is to evaluate the safety and efficacy of a platform of steerable technologies with an articulating radiofrequency ablation (RFA) probe and targeted cavity creation before vertebral augmentation in the treatment of painful spinal metastases. (2) Methods: Sixteen patients (mean age, 67 years) underwent RFA in conjunction with vertebral augmentation after the creation of a targeted balloon cavity for metastatic spinal disease and were followed up to 6 months. Pain and functional mobility were assessed before treatment and postoperatively using the Visual Analogue Score (VAS) and Functional Mobility Scale (FMS). Complications, predictability of cement distribution, anatomical restoration, and local recurrence were collected. Technical success was defined as successful intraoperative ablation and predictable cement distribution after cavity creation without major complications. (3) Results: Sixteen patients with 21 lesions were treated for tumors involving the thoracolumbar spine. All treatments were technically successful and were followed by targeted cavity creation and vertebral augmentation. A statistically significant reduction in median VAS score was observed before treatment and 1 week after RFA treatment (p < 0.001). A total of six of the seven patients who reported limited painful ambulation before treatment reported normal ambulation 1 month after treatment, while the remaining patient reported no improvement. Patients who reported wheelchair use before treatment improved to normal ambulation (four/eight) or limited painful ambulation (four/eight). The improvement in mobility before and after treatment was statistically significant (p = 0.002). Technical success was achieved in all the combined procedures. (4) Conclusions: The combined treatment of RFA and vertebral augmentation with a steerable platform that allows the creation of a targeted cavity prior to cement injection proved to be a safe and effective procedure in our patient sample, resulting in improved quality of life as assessed by the Visual Analogue Score (VAS) and Functional Mobility Scale (FMS).

A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease.

Diffuse midline glioma (DMG) is an aggressive pediatric central nervous system tumor with strong metastatic potential. As localized treatment of the primary tumor improves, metastatic disease is becoming a more important factor in treatment. We hypothesized that we could model craniospinal irradiation (CSI) through a DMG patient-derived xenograft (PDX) model and that CSI would limit metastatic tumor. We used a BT245 murine orthotopic DMG PDX model for this work. We developed a protocol and specialized platform to deliver craniospinal irradiation (CSI) (4 Gy x2 days) with a pontine boost (4 Gy x2 days) and compared metastatic disease by pathology, bioluminescence, and MRI to mice treated with focal radiation only (4 Gy x4 days) or no radiation. Mice receiving CSI plus boost showed minimal spinal and brain leptomeningeal metastatic disease by bioluminescence, MRI, and pathology compared to mice receiving radiation to the pons only or no radiation. In a DMG PDX model, CSI+boost minimizes tumor dissemination compared to focal radiation. By expanding effective DMG treatment to the entire neuraxis, CSI has potential as a key component to combination, multimodality treatment for DMG designed to achieve long-term survival once novel therapies definitively demonstrate improved local control.

Abstract 6734: Identification of the novel TENM3-ALK fusion in an AYA case with ALK rearranged neuroblastoma

Abstract Neuroblastoma is the most common extracranial solid tumor that occurs in childhood and the most common cancer in infancy. Fewer than 5% of neuroblastomas occur in adolescents and young adults (AYAs), for whom the disease has an indolent and fatal course. Chen et al. previously reported that missense mutations in the protein- tyrosine kinase domain of anaplastic lymphoma kinase (ALK) occur in approximately 10% of cases of sporadic neuroblastoma, and these missense mutations result in the activation of the ALK protein kinase domain, which plays a key role in the tumorigenic process as seen in ALK fusion proteins. Since the initial discovery of the NPM-ALK fusion protein in human anaplastic lymphoma cell lines, more than 24 different ALK fusion proteins have been discovered in various malignancies. Till date, ALK-containing chimeric proteins have not been reported in neuroblastoma. In this study, a translocation within chromosome 2p and 4q was found to bring about the formation of an in-frame fusion gene that was composed of portions of the teneurin transmembrane protein 3 (TENM3) gene and ALK gene in tumor cells from an AYA patient with neuroblastoma. The patient was 19-year-old female diagnosed with stage 4 neuroblastoma (unfavorable histology, poorly differentiated subtype, MYCN DNA not amplified). Computed tomography revealed a mass in the left adrenal gland with bone, spine, liver, and lung metastasis. ALK rearrangement was confirmed via FISH analysis. Crizotinib resulted in no disease progression for 5 months, except for metastatic spinal disease, but it did not exhibit high efficacy compared with its effects against lymphoma and lung cancer. This 5′ in-frame fusion partner gene in neuroblastoma has not yet been identified, and its role is not well-known in oncogenesis. We generated the cell line with the expression of the full length TENM3-ALK cDNA in NIH-3T3 cells led to the formation of a fusion protein. A cell-based evaluation of this predicted ALK protein variant revealed activation of downstream targets-STAT3, AKT and ERK- and ALK inhibitors, crizotinib or lorlatinib, treatment inhibited the growth of xenograft tumors with stable TENM3-ALK expression. We determined whether TENM3-ALK affects transformation and proliferation using a soft agar colony formation assay. As expected, the cells that expressed an empty vector and wild type ALK line did not produce a considerable number of colonies, whereas TENM3-ALK transfected cells showed anchorage-independent growth, resulting in the production of a higher number of colonies. The evidence for the role of ALK receptor signaling in stimulating neuroblastoma tumor cell growth and the demonstrated in vitro and in vivo efficacy of the ALK selective inhibitors in this study provide biological and clinical justification for the further exploration of this combination and testing in patients with recurrent or refractory neuroblastoma. Citation Format: Mitsuteru Hiwatari, Masafumi Seki, Ryosuke Matsuno, Kenichi Yoshida, Takeshi Nagasawa, Aiko Sato-Otsubo, Shohei Yamamoto, Motohiro Kato, Kentaro Watanabe, Masahiro Sekiguchi, Satoru Miyano, Seishi Ogawa, Junko Takita. Identification of the novel TENM3-ALK fusion in an AYA case with ALK rearranged neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6734.

Verteporfin-loaded microparticles for radiosensitization of preclinical lung and breast metastatic spine cancer.

The vertebral column is the most common site for skeletal metastasis, often leading to debilitating pain and weakness. Metastatic cancer has unique genetic drivers that potentiate tumorigenicity. There is an unmet need for novel targeted therapy in patients with spinal metastatic disease. The authors assessed the effect of verteporfin-induced yes-associated protein (YAP) inhibition on spine metastatic cell tumorigenicity and radiation sensitivity in vitro. Animal studies used a subcutaneous xenograft mouse model to assess the use of systemic intraperitoneal verteporfin (IP-VP) and intratumoral verteporfin microparticles (IT-VP) to inhibit the tumorigenicity of lung and breast spinal metastatic tumors from primary patient-derived tissue. Verteporfin led to a dose-dependent decrease in migration, clonogenicity, and cell viability via inhibition of YAP and downstream effectors cyclin D1, CTGF, TOP2A, ANDRD1, MCL-1, FOSL2, KIF14, and KIF23. This was confirmed with knockdown of YAP. Verteporfin has an additive response when combined with radiation, and knockdown of YAP rendered cells more sensitive to radiation. The addition of verteporfin to YAP knockdown cells did not significantly alter migration, clonogenicity, or cell viability. IP-VP and IT-VP led to diminished tumor growth (p < 0.0001), especially when combined with radiation (p < 0.0001). Tissue analysis revealed diminished expression of YAP (p < 0.0001), MCL-1 (p < 0.0001), and Ki-67 (p < 0.0001) in tissue from verteporfin-treated tumors compared with vehicle-treated tumors. This is the first study to demonstrate that verteporfin-mediated inhibition of YAP leads to diminished tumorigenicity in lung and breast spinal metastatic cancer cells. Targeting of YAP with verteporfin offers promising results that could be translated to human clinical trials.

Cervicothoracic junction instrumentation strategies following separation surgery for spinal metastases.

The cervicothoracic junction (CTJ) is a challenging region to stabilize after tumor resection for metastatic spine disease. The objective of this study was to describe the outcomes of patients who underwent posterolateral decompression and instrumented fusion (i.e., separation surgery across the CTJ for instability due to metastatic disease). The authors performed a single-institution retrospective study of a prospectively collected cohort of patients who underwent single-approach posterior decompression and instrumented fusion across the CTJ for metastatic spine disease between 2011 and 2018. Adult patients (≥ 18 years old) who presented with mechanical instability, myelopathy, and radiculopathy secondary to metastatic epidural spinal cord compression (MESCC) of the CTJ (C7-T1) from 2011 to 2018 were included. Seventy-nine patients were included, with a mean age of 62.1 years. The most common primary malignancies were non-small cell lung (n = 17), renal cell (11), and prostate (8) carcinoma. The median number of levels decompressed and construct length were 3 and 7, respectively. The average operative time, blood loss, and length of stay were 179.2 minutes, 600.5 ml, and 7.7 days, respectively. Overall, 58 patients received adjuvant radiation, and median dose, fractions, and time from surgery were 27 Gy, 3 fractions, and 20 days, respectively. All patients underwent lateral mass and pedicle screw instrumentation. Forty-nine patients had tapered rods (4.0/5.5 mm or 3.5/5.5 mm), 29 had fixed-diameter rods (3.5 mm or 4.0 mm), and 1 had both. Ten patients required anterior reconstruction with poly-methyl-methacrylate. The overall complication rate was 18.8% (6 patients with wound-related complications, 7 with hardware-related complications, 1 with both, and 1 with other). For the 8 patients (10%) with hardware failure, 7 had tapered rods, all 8 had cervical screw pullout, and 1 patient also experienced rod/screw fracture. The average time to hardware failure was 146.8 days. The 2-year cumulative incidence rate of hardware failure was 11.1% (95% CI 3.7%-18.5%). There were 55 deceased patients, and the median (95% CI) overall survival period was 7.97 (5.79-12.60) months. For survivors, the median (range) follow-up was 12.94 (1.94-71.80) months. Instrumented fusion across the CTJ demonstrated an 18.8% rate of postoperative complications and an 11% overall 2-year rate of hardware failure in patients who underwent metastatic epidural tumor decompression and stabilization.

Performance Assessment of the American College of Surgeons Risk Calculator in Metastatic Spinal Tumor Surgery.

This was a retrospective cohort study. The objective of this study was to assess the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator performance in patients undergoing surgery for metastatic spine disease. Patients with spinal metastases may require surgical intervention for cord compression or mechanical instability. The ACS-NSQIP calculator was developed to assist surgeons with estimating 30-day postoperative complications based on patient-specific risk factors and has been validated within several surgical patient populations. We included 148 consecutive patients at our institution who underwent surgery for metastatic spine disease between 2012 and 2022. Our outcomes were 30-day mortality, 30-day major complications, and length of hospital stay (LOS). Predicted risk, determined by the calculator, was compared with observed outcomes using receiver operating characteristic curves with area under the curve (AUC) and Wilcoxon signed-rank tests. Analyses were repeated using individual corpectomy and laminectomy Current Procedural Terminology (CPT) codes to determine procedure-specific accuracy. Based on the ACS-NSQIP calculator, there was good discrimination between observed and predicted 30-day mortality incidence overall (AUC=0.749), as well as in corpectomy cases (AUC=0.745) and laminectomy cases (AUC=0.788). Poor 30-day major complication discrimination was seen in all procedural cohorts, including overall (AUC=0.570), corpectomy (AUC=0.555), and laminectomy (AUC=0.623). The overall median observed LOS was similar to predicted LOS (9 vs. 8.5d, P =0.125). Observed and predicted LOS were also similar in corpectomy cases (8 vs. 9d; P =0.937) but not in laminectomy cases (10 vs. 7d, P =0.012). The ACS-NSQIP risk calculator was found to accurately predict 30-day postoperative mortality but not 30-day major complications. The calculator was also accurate in predicting LOS following corpectomy but not laminectomy. While this tool may be utilized to predict risk short-term mortality in this population, its clinical value for other outcomes is limited.

Implant Materials for Anterior Column Reconstruction of Cervical Spine Tumor.

The spine is the most common site of bone metastases. Many cancer patients will ultimately develop spinal metastatic disease with symptomatic epidural spinal cord compression. At present, the main treatment for cervical spine tumors is surgical resection combined with postoperative radiotherapy. Implant materials for cervical spine anterior column reconstruction need to meet amounts of different properties, such as biocompatibility, bioactivity and the ability to maintain long-term mechanical strength. The selection of different materials determines the surgical efficacy and prognosis of patients to a certain extent. This article provides an overview of a variety of implant materials used for anterior column reconstruction after cervical spine tumor resection, introduces and analyzes their properties, advantages, disadvantages, derivatives, and applications in clinical practice, and looks forward to the future development of implant materials.

Multidisciplinary Approach to Spinal Metastases and Metastatic Spinal Cord Compression—A New Integrative Flowchart for Patient Management

Metastatic spine disease (MSD) and metastatic spinal cord compression (MSCC) are major causes of permanent neurological damage and long-term disability for cancer patients. The development of MSD is pathophysiologically framed by a cooperative interaction between general mechanisms of bone growth and specific mechanisms of spinal metastases (SM) expansion. SM most commonly affects the thoracic spine, even though multiple segments may be affected concomitantly. The great majority of SM are extradural, while intradural-extramedullary and intramedullary metastases are less frequently seen. The management of patients with SM is particularly complex and challenging, with multiple factors-such as the spinal stability status, primary tumor radio and chemosensitivity, cancer biological burden, patient performance status and comorbidities, and patient's oncological prognosis-influencing the clinical decision-making process. Different frameworks were developed in order to systematize and support this process. A multidisciplinary, personalized approach, enriched by the expertise of each involved specialty, is crucial. We reviewed the most recent evidence and proposed an updated algorithmic approach to patients with MSD according to the clinical scenario of each patient. A flowchart-based approach offers an evidence-based management of MSD, providing a valuable clinical decision tool in a context of high uncertainty and quick-acting need.

Posterior-only approach in patients with poor general condition and spinal metastatic vertebral fracture

PurposeThe surgical treatment of spinal metastases is mostly palliative in nature and focuses on improving the quality of life of patients. The posterior transpedicular surgical approach provides circumferential 360° decompression, allows reconstruction and stabilisation to be achieved in a single session and can be performed using an open, mini-open or minimally invasive approach. We present and discuss the surgical techniques and outcomes for patients with single-level metastatic spinal disease and in poor general condition who underwent surgery via the posterior-only transpedicular corpectomy approach and reconstruction with expandable corpectomy cages. MethodsPatients with a single level thoracolumbar metastatic disease (T3-L5) and a Karnofsky score of ≤70, who underwent a complete posterior transpedicular corpectomy with expandable cage reconstruction of the anterior spinal column were retrospectively reviewed. Patients’ demographics, SINS, modified Tokuhashi scores as well as preoperative and postoperative ASIA scale, Karnofsky scores, VAS scores and vertebral height/Cobb angle values were analysed. ResultsA total of 44 patients (24 M/20 F) (mean age 53.25±21.26 years) met the inclusion criteria. The modified Tokuhashi scores were as follows: score 0–8, 5 (11.4%) patients; score 9–11, 14 (31.8%) patients; and score 12–15, 25 (56.8%) patients. There were significant improvements in the postoperative VAS scores (mean 7.7–2.9), Karnofsky scores (mean 63.3–79.6) as well as the Cobb angles (18.6–12.8°) and vertebral height. Thirtyfive patients showed improved neurological function by at least one ASIA grade, whereas 9 showed no improvement during the postoperative period. ConclusionsThis technique, which has a low complication rate and a short recovery time, can help achieve satisfactory results even in patients with poor metabolic profiles and Karnofsky scores in the preoperative period. Further clinical studies with large patient groups are warranted to confirm the results of this study.

Preoperative Serum Albumin Level Predicts Length of Stay and Perioperative Adverse Events Following Vertebral Corpectomy and Posterior Stabilization for Metastatic Spine Disease.

Retrospective review of a prospectively collected national database. To determine the association between preoperative serum albumin levels and perioperative adverse events (AEs) following vertebral corpectomy and posterior stabilization for metastatic spine disease. The 2010 to 2019 American College of Surgeons' National Surgical Quality Improvement (ACS-NSQIP) database was used to identify all patients undergoing vertebral corpectomy and posterior stabilization for metastatic spine disease. Receiver operative characteristic (ROC) curve analysis was used to determine preoperative serum albumin cut-off values for predicting perioperative AEs. Low preoperative serum albumin was defined as serum albumin below this cut-off value. A total of 301 patients were included in the study. ROC curve analysis demonstrated serum albumin < 3.25g/dL as a cut-off value for predicting perioperative AEs. The low serum albumin group had a higher overall perioperative AEs (P = .041), longer post-operative LOS (P < .001), higher 30-day reoperation rate (P = .014), and a higher in-hospital mortality rate (P = .046). Multivariate analysis demonstrated that low preoperative serum albumin was associated with higher perioperative AEs. Low serum albumin level is associated with higher perioperative AEs, longer postoperative LOS, and higher rates of 30-day reoperation and in-hospital mortality among patients undergoing vertebral corpectomy and posterior stabilization for metastatic spine disease. Strategies to improve preoperative nutritional status in patients undergoing this procedure may improve these perioperative outcome measures within this surgical population. III.

Preoperative Predictors of Survival in Patients With Spinal Metastatic Disease.

There remains a number of factors thought to be associated with survival in spinal metastatic disease, but evidence of these associations is lacking. In this study, we examined factors associated with survival among patients undergoing surgery for spinal metastatic disease. We retrospectively examined 104 patients who underwent surgery for spinal metastatic disease at an academic medical center. Of those patients, 33 received local preoperative radiation (PR) and 71 had no PR (NPR). Disease-related variables and surrogate markers of preoperative health were identified, including age, pathology, timing of radiation and chemotherapy, mechanical instability by spine instability neoplastic score, American Society of Anesthesiologists (ASA) classification, Karnofsky performance status (KPS), and body mass index (BMI). We performed survival analyses using a combination of univariate and multivariate Cox proportional hazards models to assess significant predictors of time to death. Local PR (Hazard Ratio [HR] = 1.84, P = 0.034), mechanical instability (HR = 1.11, P = 0.024), and melanoma (HR = 3.60, P = 0.010) were significant predictors of survival on multivariate analysis when controlling for confounders. PR vs NPR cohorts exhibited no statistically significant differences in preoperative age (P = 0.22), KPS (P = 0.29), BMI (P = 0.28), or ASA classification (P = 0.12). NPR patients had more reoperations for postoperative wound complications (11.3% vs 0%, P < 0.001). In this small sample, PR and mechanical instability were significant predictors of postoperative survival, independent of age, BMI, ASA classification, and KPS and in spite of fewer wound complications in the PR group. It is possible that PR was a surrogate of more advanced disease or poor response to systemic therapy, independently portending a worse prognosis. Future studies in larger, more diverse populations are crucial for understanding the relationship between PR and postoperative outcomes to determine the optimal timing for surgical intervention. These findings are clinically relevent as they provide insight into factors associated with survival in metastatic spinal disease.

The use of red flags during the referral chain of patients surgically treated for symptomatic spinal metastases.

The use of so-called "red flags" may be beneficial in identifying patients with metastatic spinal disease. This study examined the utility and efficacy of these red flags in the referral chain of patients surgically treated for spinal metastases. The referral chains from the onset of symptoms until surgical treatment for all patients receiving surgery for spinal metastases between March 2009 and December 2020 were reconstructed. The documentation of red flags, as defined by the Dutch National Guideline on Metastatic Spinal Disease, was assessed for each healthcare provider involved. A total of 389 patients were included in the study. On average, 33.3% of red flags were documented as present, 3.6% were documented as absent, and 63.1% were undocumented. A higher rate of red flags documented as present was associated with a longer time to diagnosis, but a shorter time to definitive treatment by a spine surgeon. Moreover, red flags were documented as present more often in patients who developed neurological symptoms at any point during the referral chain than those who remained neurologically intact. The association of red flags with developing neurological deficits highlights their significance in clinical assessment. However, the presence of red flags was not found to decrease delays prior to referral to a spine surgeon, indicating that their relevance is currently not sufficiently recognized by healthcare providers. Raising awareness of symptoms indicative of spinal metastases may expedite timely (surgical) treatment and thus improve treatment outcome.

Perception of frailty in spinal metastatic disease: international survey of the AO Spine community.

Frailty has not been clearly defined in the context of spinal metastatic disease (SMD). Given this, the objective of this study was to better understand how members of the international AO Spine community conceptualize, define, and assess frailty in SMD. The AO Spine Knowledge Forum Tumor conducted an international cross-sectional survey of the AO Spine community. The survey was developed using a modified Delphi technique and was designed to capture preoperative surrogate markers of frailty and relevant postoperative clinical outcomes in the context of SMD. Responses were ranked using weighted averages. Consensus was defined as ≥ 70% agreement among respondents. Results were analyzed for 359 respondents, with an 87% completion rate. Study participants represented 71 countries. In the clinical setting, most respondents informally assess frailty and cognition in patients with SMD by forming a general perception based on clinical condition and patient history. Consensus was attained among respondents regarding the association between 14 preoperative clinical variables and frailty. Severe comorbidities, extensive systemic disease burden, and poor performance status were most associated with frailty. Severe comorbidities associated with frailty included high-risk cardiopulmonary disease, renal failure, liver failure, and malnutrition. The most clinically relevant outcomes were major complications, neurological recovery, and change in performance status. The respondents recognized that frailty is important, but they most commonly evaluate it based on general clinical impressions rather than using existing frailty tools. The authors identified numerous preoperative surrogate markers of frailty and postoperative clinical outcomes that spine surgeons perceived as most relevant in this population.

A Comparison of Prognostic Models to Facilitate Surgical Decision-Making for Patients With Spinal Metastatic Disease.

Retrospective cohort. Compare the performance of and provide cutoff values for commonly used prognostic models for spinal metastases, including Revised Tokuhashi, Tomita, Modified Bauer, New England Spinal Metastases Score (NESMS), and Skeletal Oncology Research Group model, at three- and six-month postoperative time points. Surgery may be recommended for patients with spinal metastases causing fracture, instability, pain, and/or neurological compromise. However, patients with less than three to six months of projected survival are less likely to benefit from surgery. Prognostic models have been developed to help determine prognosis and surgical candidacy. Yet, there is a lack of data directly comparing the performance of these models at clinically relevant time points or providing clinically applicable cutoff values for the models. Sixty-four patients undergoing surgery from 2015 to 2022 for spinal metastatic disease were identified. Revised Tokuhashi, Tomita, Modified Bauer, NESMS, and Skeletal Oncology Research Group were calculated for each patient. Model calibration and discrimination for predicting survival at three months, six months, and final follow-up were evaluated using the Brier score and Uno's C, respectively. Hazard ratios for survival were calculated for the models. The Contral and O'Quigley method was utilized to identify cutoff values for the models discriminating between survival and nonsurvival at three months, six months, and final follow-up. Each of the models demonstrated similar performance in predicting survival at three months, six months, and final follow-up. Cutoff scores that best differentiated patients likely to survive beyond three months included the Revised Tokuhashi score=10, Tomita score=four, Modified Bauer score=three, and NESMS=one. We found comparable efficacy among the models in predicting survival at clinically relevant time points. Cutoff values provided herein may assist surgeons and patients when deciding whether to pursue surgery for spinal metastatic disease. 4.

THE SORG NOMOGRAM DOES NOT ACCURATELY PREDICT THREE- AND 12-MONTH SURVIVAL FOR PATIENTS WITH SPINAL METASTATIC DISEASE IN NEW ZEALAND

Several different algorithms attempt to estimate life expectancy for patients with metastatic spine disease. The Skeletal Oncology Research Group (SORG) has recently developed a nomogram to estimate survival of patients with metastatic spine disease. Whilst the use of the SORG nomogram has been validated in the international context, there has been no study to date that validates the use of the SORG nomogram in New Zealand. This study aimed to validate the use of the SORG nomogram in Aotearoa New Zealand.We collected data on 100 patients who presented to Waikato Hospital with a diagnosis of spinal metastatic disease. The SORG nomogram gave survival probabilities for each patient at each time point. Receiver Operating Characteristic (ROC) Area Under Curve (AUC) analysis was performed to assess the predictive accuracy of the SORG score. A calibration curve was also performed, and Brier scores calculated. A multivariate Cox regression analysis was performed.The SORG score was correlated with 30 day (AUC = 0.72) and 90-day mortality (AUC = 0.71). The correlation between the SORG score and 90-day mortality was weaker (AUC = 0.69). Using this method, the nomogram was correct for 79 (79%) patients at 30-days, 59 patients (59%) at 90-days, and 42 patients (42%) at 365-days. Calibration curves demonstrated poor forecasting of the SORG nomogram at 30 (Brier score = 0.65) and 365 days (Brier score = 0.33). The calibration curve demonstrated borderline forecasting of the SORG nomogram at 90 days (Brier score = 0.28). Several components of the SORG nomogram were not found to be correlated with mortality.In this New Zealand cohort the SORG nomogram demonstrated only acceptable discrimination at best in predicting life 30-, 90- or 356-day mortality in patients with metastatic spinal disease.

Wound complications in metastatic spine tumor patients with and without preoperative radiation.

Wound complications are a common adverse event following metastatic spine tumor surgery. Some patients with spinal metastases may first undergo radiation but eventually require spinal surgery because of either cord compression or instability. The authors compared wound complication rates in patients who had undergone surgery for metastatic disease and received preoperative radiation treatments, postoperative radiation, or no radiation. Records from patients treated at the University of California, San Francisco, for metastatic spine disease between 2005 and 2017 were retrospectively reviewed. Baseline characteristics were collected, including preoperative Karnofsky Performance Status (KPS), Spine Instability Neoplastic Score, total radiation dose, indication for surgery, diabetes status, time between radiation and surgery, use of perioperative chemotherapy or steroids, estimated blood loss, extent of fusion, and preoperative albumin level. Wound complication was defined as poor healing, dehiscence, or infection per the Centers for Disease Control and Prevention guidelines, within 6 months of surgery. One-way ANOVA was used to compare means across groups. Cumulative incidence analysis with competing risk methodology was used to adjust for risk of death during follow-up. Statistical analysis was performed using R software. Two hundred five patients with adequate medical records were identified. Seventy patients had received preoperative radiation, 74 had received postoperative radiation within 6 months after surgery, and 61 had received no radiation at the surgical site. Wound complication rates were similar across the 3 cohorts: 14.3% (n = 10) in the group with preoperative radiation, 10.8% (n = 8) in the group that received postoperative radiation, and 11.5% (n = 7) in the group with no radiation (p = 0.773). Competing risk analysis showed a higher cumulative incidence of wound complications for the preoperative cohort, though this difference was not significant (p = 0.46). Overall, 89 patients were treated with external beam radiation therapy (EBRT), whereas 55 received stereotactic body radiation therapy (SBRT). There was no significant difference in wound complications for patients treated with EBRT (11.2%, n = 10) versus SBRT (14.5%, n = 8; p = 0.825). KPS was the only factor correlated with wound complications on univariate analysis (p = 0.03). Wound complication rates did not differ across the 3 cohorts: patients treated with preoperative radiation, postoperative radiation within 6 months of surgery, or no radiation. The effect size was small for KPS and likely does not represent a clinically significant predictor of wound complications.

Role of Decompressive Surgery in Neurologically Intact Patients with Low to Intermediate Intraspinal Metastatic Tumor Burden.

Surgical decompression (SD) followed by radiotherapy (RT) is superior to RT alone in patients with metastatic spinal disease with epidural spinal cord compression (ESCC) and neurological deficit. For patients without neurological deficit and low- to intermediate-grade intraspinal tumor burden, data on whether SD is beneficial are scarce. This study aims to investigate the neurological outcome of patients without neurological deficit, with a low- to intermediate-ESCC, who were treated with or without SD. This single-center, multidepartment retrospective analysis includes patients treated for spinal epidural metastases from 2011 to 2021. Neurological status was assessed by Frankel grade, and intraspinal tumor burden was categorized according to the ESCC scale. Spinal instrumentation surgery was only considered as SD if targeted decompression was performed. ESCC scale was determined in 519 patients. Of these, 190 (36.6%) presented with no neurological deficit and a low- to intermediate-grade ESCC (1b, 1c, or 2). Of these, 147 (77.4% were treated with decompression and 43 (22.65%) without. At last follow-up, there was no difference in neurological outcome between the two groups. Indication for decompressive surgery in neurologically intact patients with low-grade ESCC needs to be set cautiously. So far, it is unclear which patients benefit from additional decompressive surgery, warranting further prospective, randomized trials for this significant cohort of patients.

Kyphoplasty versus vertebroplasty cement extravasation and outcomes in patients with metastatic spinal disease

Kyphoplasty versus vertebroplasty cement extravasation and outcomes in patients with metastatic spinal disease

Implant failure after stabilization surgery in spinal metastatic disease: Investigation of potential risk factors in a single center’s outcome analysis

Implant failure after stabilization surgery in spinal metastatic disease: Investigation of potential risk factors in a single center’s outcome analysis

Spinal Metastases and the Evolving Role of Molecular Targeted Therapy, Chemotherapy, and Immunotherapy.

Metastatic involvement of the spine is a common complication of systemic cancer progression. Surgery and external beam radiotherapy are palliative treatment modalities aiming to preserve neurological function, control pain and maintain functional status. More recently, with development of image guidance and stereotactic delivery of high doses of conformal radiation, local tumor control has improved; however recurrent or radiation refractory disease remains a significant clinical problem with limited treatment options. This manuscript represents a narrative overview of novel targeted molecular therapies, chemotherapies, and immunotherapy treatments for patients with breast, lung, melanoma, renal cell, prostate, and thyroid cancers, which resulted in improved responses compared to standard chemotherapy. We present clinical examples of excellent responses in spinal metastatic disease which have not been specifically documented in the literature, as most clinical trials evaluate treatment response based on visceral disease. This review is useful for the spine surgeons treating patients with metastatic disease as knowledge of these responses could help with timing and planning of surgical interventions, as well as promote multidisciplinary discussions, allowing development of an individualized treatment strategy to patients presenting with widespread multifocal progressive disease, where surgery could lead to suboptimal results.